Fludarabine Phosphate, Cytarabine, Filgrastim-sndz, Gemtuzumab Ozogamicin, and Idarubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

PRIMARY OBJECTIVES:

I. Evaluate the safety of a regimen incorporating fludarabine phosphate (fludarabine),
high-dose cytarabine, filgrastim-sndz, gemtuzumab ozogamicin and idarubicin hydrochloride
(idarubicin) in patients with untreated inv(16) or t(8;21) acute myeloid leukemia (AML).

II. Evaluate the complete remission rates achieved in this population with this regimen.

SECONDARY OBJECTIVES:

I. Assess the proportion of patients with untreated inv(16) or t(8;21) AML who, having
entered complete remission (CR) on this regimen, remain alive in CR two years from CR date.

II. Assess whether the quantitative polymerase chain reaction (Q-PCR) results can be used in
detecting relapse in these patients.

OUTLINE:

REMISSION INDUCTION: Patients receive filgrastim-sndz subcutaneously (SC) once daily (QD)
beginning on day -1 and continuing until blood count recovery. Patients also receive
fludarabine phosphate intravenously (IV) over 30 minutes on days 1-5, cytarabine IV over 4
hours on days 1-5, gemtuzumab ozogamicin IV over 2 hours on day 1, and idarubicin
hydrochloride IV over 30 minutes on days 3 and 4. Patients not in remission after their first
induction therapy may repeat remission induction therapy.

POST-REMISSION THERAPY: Patients receive filgrastim-sndz SC on day -1, fludarabine phosphate
IV over 30 minutes on days 1-3, cytarabine IV over 4 hours on days 1-3, gemtuzumab ozogamicin
IV over 2 hours on day 1 of courses 1 or 2 and 5 or 6, and idarubicin hydrochloride IV over
30 minutes on days 2 and 3 (day 2 only of courses 3-6). Treatment repeats every 4-6 weeks for
up to 6 courses in the absence of disease progression or unacceptable toxicity.

FURTHER MODIFICATION OF POST-REMISSION THERAPY: Patients older than 60, with significant
comorbidities, experiencing life-threatening complications, prolonged cytopenias, or not
achieving complete molecular response may receive decitabine IV daily for 5 days after
discussion with the principal investigator. Treatment repeats every 4-6 weeks for up to 12
courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years.

Inclusion Criteria:

- Patients must have untreated AML, or high-risk myelodysplastic syndromes (MDS)
(refractory anemia with excess blasts, [RAEB], or RAEB "in transformation" [RAEB-t])
characterized by t(8;21), inv(16), or t(16;16); the presence of additional
abnormalities is irrelevant

- Patients must provide written consent

- Participants will not be excluded based on performance status; for patients with
Eastern Cooperative Oncology Group (ECOG) performance status >= to 3 the dosing
schedule will be discussed with study chairman

- Patients with organ dysfunction will not be excluded from the study; for patients with
evidence of organ dysfunction (creatinine >= 1.5, cardiac ejection fraction =< 50%,
total bilirubin >=2 and aspartate aminotransferase [AST]/alanine aminotransferase
[ALT] >= 3 times upper limit of normal [ULN]), dose adjustments/omissions will be made

- Up to one cycle of prior induction therapy will be permitted to include patients in
whom presence of "good-risk" cytogenetics was initially missed; if the patient is in
remission from induction therapy, he/she will receive post-remission therapy; if the
patient is not in remission then he/she will receive induction therapy

- Patients of child bearing potential should practice effective methods of contraception

Exclusion Criteria:

- Pregnant and lactating females will be excluded